The objective of the proposed research is to clarify mechanisms by which host immune responses influence the proliferation of myeloma tumor cells, and the means by which these cells evade destruction by suppressive immune responses. Because BALB/c mice can make antibodies to unique, idiotypic determinants of some myeloma proteins of BALB/c origin, and because this immune response (or perhaps an accompanying cell-mediated immunity of similar specificity) can suppress the proliferation of some BALB/c myeloma tumors in BALB/c hosts, attempts will be made to evaluate myeloma proteins as "tumor-specific transplantation antigens". The distribution and orientation of these proteins in the cell membranes of various tumors will be analyzed, and immune responses will be used to select for myeloma tumor variants that resist cytotoxic immune attack; resistant and susceptible variants will be compared with respect to various cell membrane properties. This approach will be extended to other distinctive antigens in the surface membranes of myeloma tumor cells. Cytotoxic thymus-derived lymphocytes (Tk cells) that specifically destroy various myeloma tumors will also be used to study antigens of the myeloma cell surface. BIBLIOGRAPHIC REFERENCES: Janeway, C.A.; Sakato, N. and Eisen, H.N. Recognition of Immunoglobulin Idiotypes by Thymus-Derived Lymphocytes. Proc.Nat. Acad.Sci.U.S.A. 72: 2357-2360 (1975). Sakato, N.; Janeway, C.A. and Eisen, H.N. Antibodies to Idiotypes of Isologous Immunoglobulins: Implications for Immune Networks and Multispecificity. Cold Spring Harbor Symposium for Quantitative Biology (1976), in press.